Whether early treatment of SIV infection can delay immune destruction allowing time for developing more effective protection is pertinent now that more effective treatment is available. We studied infected monkeys surviving long-term after treatment with (R)-9-(2-phosphonyl-methoxypropyl) adenine (PMPA). Two of 5 monkeys treated for 28 days beginning 24 hours after SIV inoculation survived over 1,069 days. Infection establishment was prevented since virus could not be isolated; provirus could not be detected; antibodies did not develop; and lymphocyte subsets remained stable. Five other monkeys received long-term PMPA treatment beginning 14 days after SIV infection. A strong antiviral effect occurred in 3/5 monkeys. After only 7 days of treatment plasma virus decreased an average of 3.4 logs (99.8%). A much weaker antiviral effect was observed in 2 other monkeys which after 7 days treatment had decreases of only 1.2 logs (93.7%). Treatment was stopped in 3 of these monkeys af ter 448 to 469 days. In 1 monkey which had high plasma viral RNA levels throughout treatment, the RNA level only increased 0.6 log after cessation. A sharp decrease in CD4+ cells after treatment stopped suggested that treatment had exerted a protective effect even though the plasma viral RNA had not decreased to low levels. In another monkey the plasma SIV RNA had been held below quantifiable levels by PMPA; stopping treatment resulted in marked increases in plasma viral RNA, proviral DNA, and antigenemia accompanied by rapidly decreasing CD4+ cells. The third monkey showed only a slight increase in plasma viral RNA after treatment cessation that did not progress, and CD4+ cells remained stable. The latter 2 monkeys remain alive 586 days after stopping treatments. Their long survival suggests that early treatment may allow development of protective mechanisms which may prolong survival even after treatments cease. FUNDING NIH-N01-AI-15119 PUBLICATIONS None